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Andrea Richardson, MD, PhD
Associate Professor of Pathology
Johns Hopkins University School of Medicine
- Seeking to understand the phenomenon of DNA repair deficiency and how it leads to cancer.
- Laboratory studies are conducted to determine how mutations in DNA repair genes affect the gene mutation profile of tumor cells and response to anti-cancer drugs.
- These studies will provide new information that will help predict which treatment will work best for a specific tumor.
Breast cancers caused by mutations in the BRCA genes have a defect in how the cells repair DNA damage. This makes them sensitive to certain drugs such as a new class of drugs called PARP inhibitors and platinum-based chemotherapy. Dr. Richardson is conducting laboratory studies to understand how mutations in BRCA genes leads to other defects in DNA repair that might also be targeted with new drugs.
Full Research Summary
Mutations in the BRCA1 gene result in deficient DNA repair processes that predispose mutation carriers to an increased risk of breast cancer.
BRCA1-driven breast cancers are most likely to be of the triple negative subtype (TNBC) and are more likely to respond to certain types of chemotherapy. Understanding how these cancers develop and whether mutation in other DNA repair genes results in similar cancers with similar drug sensitivities is the ultimate goal of Dr. Richardson's BCRF research.
Her team recently demonstrated that a complete loss of the BRCA gene results in widespread mutations in other genes –what she calls a "mutator phenotype", while cells with just partial loss of BCRA are mostly normal.
This year, her team will delve deeper into this phenomenon to determine what other factors are at play and whether mutations in other DNA repair genes cause a similar "mutation phenotype". As part of this work they are creating a tumor database and tissue archive for use in future breast cancer research and developing a clinical assay for predicting chemotherapy responses in patients with triple negative breast cancers.
Collectively, these studies will lead to better risk assessment and better outcomes in breast cancer through more personalized patient care.
Dr. Andrea L. Richardson is an Associate Professor of Pathology and Director of the Pathology Community Practice Division at Johns Hopkins University School of Medicine, where she moved in 2015 after more than eight years on the faculty of Brigham and Women's Hospital, Harvard Medical School in Boston. She maintains an active clinical practice on the breast pathology consultation service. Her research focus is breast cancer genetics and pathobiology. She is actively engaged in translational breast cancer research, frequently with multi-disciplinary teams. Dr. Richardson has extensive experience in tissue-based molecular assays. Her laboratory research has focused on characterizing the molecular aberrations in subtypes of breast cancer important for pathogenesis, tumor progression, and tumor response to therapy.
BCRF Investigator Since
The A Cure in Our Lifetime Award